1. Field of the Invention
The invention relates to naphthalene derivatives which are useful in inhibiting certain dermatological conditions and inhibiting lipoxygenase activity, particularly 5-lipoxygenase activity which makes the compounds useful for topical treatment of inflammatory states. This invention also relates to pharmaceutical compositions useful in relieving the effects of certain chronic recurrent papulosquamous dermatoses, e.g., psoriasis. This invention also relates to a process for preparing compounds of this invention.
2. Related Disclosures
Psoriasis is a skin disease characterized in part by excessive proliferation of cells of the epidermis which remain strongly adherent and build up into a scaley plaque typical of the disease. Currently available therapies, which are not curative, depend on the control of epidermal cell proliferation through the use of hormonal agents, such as corticosteroids or through the use of compounds related to cancer chemotherapy such as hydroxyurea, methotrexate, and the nitrogen mustards.
While the above agents are effective to a certain extent, they cause numerous severe undesirable side effects including renal irritation, hepatic toxicity, and erythema.
The compound, 2,3-dimethoxy-1,4-diacetyloxynaphthalene is known and is disclosed to be useful as a synthetic intermediate, but no useful biological activity has been ascribed to it. See J. Chem. Res., Synop. 1980(4), 156-7 and An. Quim. 1976, 72(3):247-53. Certain diester naphthalenes are known to be useful in treating psoriasis. See, for example, U.S. Pat. No. 4,466,981. Surprisingly, it has been discovered that the compounds of the instant invention are also effective antipsoriatic agents. Compounds of formula (Ib) and (Ic), infra, provide prolonged activity in the treatment of psoriasis because of their stability upon application and slow conversion to compounds of formula (Ia). Further, the compounds of the present invention are more stable in the topical formulations normally used.